Sensitive and fast assessment of DNA methylation degree by a luminescent lanthanide-functionalized MOF probe

5-Methylcytosine (5-mC), as one of the primary forms of DNA methylation, plays essential roles in a variety of biological activities. Its rapid and precise detection is therefore paramount for abnormal DNA methylation assessment, but still remains challenging. Herein, a highly luminescent and stable lanthanide-based metal-organic framework (MOF) probe, namely Eu-ZrMOF, is firstly designed for qualitative and quantitative analysis of 5-mC, wherein the organic building units of 1,3,5-benzenetricarboxylic acid (BTC) serve as both the energy donors and recognition molecules, and the modified Eu 3+ ions function as intense signal reporters. Significantly, the luminescence of the fabricated Eu-ZrMOF probe can be remarkably quenched by 5-mC via its inner filter effect on the BTC absorption, achieving high response to 5-mC in a very short time (20 s). Moreover, such an efficient, instantaneous response probe presents excellent specificity towards 5-mC among various coexisting species in urine, and high sensitivity with a linear detection range of 0–200 μM and limit of detection (LOD) of 0.18 μM, thereby enabling it to be applied in accurately quantifying 5-mC content in real urine samples with high recoveries (95.5–98.5 %) and low relative standard deviations (< 2.5 %). This study demonstrates a simple, fast and effective approach for sensitive identification of urinary 5-mC, prefiguring its great potential for the assessment of DNA methylation associated with genetic diseases and tumors.